Coordination Chemistry of Potentially S,N,Npy-Tridentate Thiosemicarbazones with the {Re(CO)3}+ Fragment and Formation of Hemiaminal Derivatives

Nine potentially S,N,Npy-tridentate thiosemicarbazones (HL) derived from pyridine-2-carbaldehyde or 1-(2-pyridyl)ethanone have been prepared and fully characterized. The X-ray crystal structures of six of them and two hydrochlorides were determined and analyzed. The reaction of the [ReX(CH3CN)2(CO)3]/[ReX(CO)5] (X = Cl and Br) precursors with these ligands yielded different kinds of compounds: the adducts [ReX(HL)(CO)3], in which the ligands were S,N-bidentate; the trinuclear species [Re3Cl2(L23)(HL23)(CO)9]; and the thiosemicarbazonate compounds [Re(L)(CO)3], where the ligand is S,N,Npy-tridentate. Besides, the reaction in methanol or ethanol of the thiosemicarbazones derived from aldehydes yielded S,N,Npy-tridentate hemiaminal cationic [Re(HLOR)(CO)3]X and neutral [Re(LOMe)(CO)3] complexes after the coordinated ligand underwent addition of the alcohol group to the imine bond. The reactivity of the complex [ReX(HL)(CO)3] in MeOH and NEt3 led to the formation of dinuclear [Re2(L)2(CO)6], where the thiosemicarbazonate is again S,N-bidentate. The influence that the substituents on the thiosemicarbazone ligands have on the stability of the complexes and the effect of the reaction medium on the resulting compounds have been analyzed.


Crystal and molecular structures of the free ligands
The X-ray structures of the ligands HL 11 , HL 12 , HL 22 , HL 23 and of the two isomers of HL 13 and the hydrochlorides of HL 13 and HL 23 were determined and the molecular structures are shown in Figure S1.
A selection of the main distances and angles are listed in Table S2.
The system related to HL 13 will be discussed in greater detail due to the availability of more structural information, but it must be taken into account that, in principle, the structures of the rest of the ligands follow patterns common to all of them. The X-ray structure of HL 34 will be discussed separately (vide infra) since the crystal contains the zwitterionic form.
In the first instance, and setting aside aside HL 13 derivatives, all of the compounds including those that crystallize with different solvent molecules (such as HL 12 .2H 2 O and HL 11 .(C 3 H 6 O)) show a predominance in the thiosemicarbazone chain of the E,E,E,Z conformation, which appears to be independent of the nature of the substituents on the N1 and C2 atoms.
More variation seems to exist in the relative position of the pyridine nitrogen (N4), which is normally dependent on the presence or absence of hydrogen bond donor groups. Typically, when groups with hydrogen bond donor/acceptor capacity are present in the crystal, either water molecules, as in HL 12 .2H 2 O, or the phenyl OH group of another neighboring thiosemicarbazone molecule, as in HL 11 , lead the pyridine ring to orient its N4 group in a converging direction for the formation of three-center hydrogen bonds (Figures S1a and S1b). Even in the absence of this interaction, the pyridine ring is practically coplanar with the thiosemicarbazone arm. The bond distances and angles in the thiosemicarbazide fragment are, as one would expect, consistent with some delocalization of the multiple bond along the chain. 1,2 However, the C1-S1, C2-N3, N2-N3 and N2-C1 distances suggest that, in spite of the delocalization, the canonical form depicted in Scheme 1 (see manuscript) is predominant.
The isolation of crystals of the two configurational isomers of HL 13 and the hydrochloride allows a comparative study of the effect of the relative distribution of the different groups on the most widely used structural parameters in the study of metalated compounds.
In the crystal obtained from chloroform, HL 13 (Z) has the Z conformation for the formal double bond C2=N3. This conformation is probably favored by the presence of an intramolecular hydrogen bond (S(6)) involving the hydrazine group N2-H and the pyridine nitrogen N4 ( Figure S1d). These two groups are involved in the intramolecular bond and the molecules can only associate through the interaction of the thioamidic N1-H group and sulfur (Table S3). It is interesting to note that, despite this, the molecules manage to pack more efficiently than in the HL 13 (E) isomer obtained from solutions in MeOH (as suggested by the higher density of the crystal in the Z isomer, 1.383 Mg/m 3 , compared to that of the E isomer, 1.326 Mg/m 3 , Table S1). The existence of disorder in HL 13 (E) in the ring attached to the S-8 N1 nitrogen is also consistent with this observation. In the latter structure, the pyridine nitrogen is oriented in a divergent/parallel disposition with respect to the thiosemicarbazone chain ( Figure S1c) and the molecules associate in the crystal through N2-H…N4 interactions.
In the hydrochloride [H 2 L 13 ]Cl the observed conformation is again EEEZ ( Figure S1e), with the nitrogen N4 being protonated and the chloride anion associating with the thiosemicarbazinium cation via a double 'forked' hydrogen bond N4-H…Cl and N1-H…Cl. The molecular structure is very reminiscent of that already described for the cases of the hydrate HL 12 and acetone solvate HL 11 . It is important to note that although the values of the standard deviations do not allow differences to be discerned in the values of the bond distances in the TSC arm between the E and Z conformers, there are significant differences between the bonding distances in [H 2 L 13 ] + and HL 13 (E). For example, the N2-N3 distance is significantly shorter in the hydrochloride versus the two unprotonated isomers. Furthermore, S1-C1 and C2-N3 are longer and N1-C1 and N2-C2 are shorter (Table S2)

Synthesis of pyridine thiosemicarbazone ligands
The corresponding thiosemicarbazide TSZ n and pyridine derivative xPy, were dissolved and the mixture refluxed, occasionally after added some drops of acetic acid. Then the solution was concentrated under vacuum to almost dryness and it was added diethyl ether to recover its initial volume before storing at 4 °C. Solid formed was filtered off, washed with the corresponding solvent and vacuum dried on CaCl 2 /KOH. Reagents amounts and synthetic conditions are collected in Table S3.                  fac-[ReCl(CH 3 CN) 2 (CO) 3 ] (89 mg, 0.15 mmol) and HL 11 (42 mg; 0.15 mmol) were mixed on MeOH (10 mL) and the solution refluxed for two hours. Then it was added a suspension of NaOH (9 mg; 0.23 mmol) in 3 mL of the same solvent and refluxed for 1 hour more. The resulting solution was concentrated to half its initial volume and stored at 4 °C after adding chloroform. Crystalline phase formed was filtered off, washed with water and vacuum dried on CaCl 2 /KOH.

11e·3/4(CHCl 3 ):
IR (top) and 1 H-NMR spectra in DMSO-d 6 (bottom). fac-[ReCl(CH 3 CN) 2 (CO) 3 ] (47 mg, 0.12 mmol) and HL 23 (52 mg; 0.17 mmol) were dissolved on CHCl 3 (10 mL) and the solution refluxed for three hours. The resulting solution was concentrated to half its initial volume and stored at 4 °C. The first solid formed was the chlorohydrate salt of ligand (A). The second fraction crystallized (B) was filtered off and vacuum dried on CaCl 2 /KOH.  In a NMR tube the 13b complex was dissolved on MeOD, and NEt 3 was added (about 15 eq). The signals pattern of the product 13f appeared while the 13b signals disappear of the spectrum. A small portion of crystals was isolated that allowed characterization by X-ray diffraction and infrared spectroscopy and confirmed the formation of the dimer. The 1 H-NMR shows two set of signals.